Welcome, everyone. Good afternoon, to the second day of the Citizens JMP Life Sciences Conference. It's my pleasure to introduce Cue Biopharma. Presenting for the company is Dan Passeri, CEO, and Anish Suri, President and CSO. Thank you both for being here. Appreciate that.
Right.
I never know exactly who's in the audience or who's listening to our webcast, whether they know the Cue Biopharma story or not. And so I always like to start with, you know, maybe a 2-5-minute overview of what the company's about before we jump into specific questions.
Sure. Appreciate it. No, I'll make it closer to two minutes than five minutes.
No worries.
All right. So first, I just want to thank you, Wren and JMP, for giving us the opportunity to present. So, just to remind everyone, Cue Biopharma is a publicly listed company. The symbol is CUE. This slide just have a couple of concept slides here. And what this conveys is really the emphasis of our approach is to reestablish immune balance. And we have a protein engineering platform that basically enables us to target particular cell lineages that are needed to address some imbalance that's affecting health. In the case of oncology, T cells, which is in essence the heavy artillery of the immune system, are not activated effectively against cancer. Cancer has either evaded it through protective measures such as checkpoints and anti-inflammatory processes, or the T cells are exhausted.
So when cancer manifests as disease, it in essence is escaping the surveillance and attack of the immune system. So in oncology, the objective is to stimulate cancer-relevant or cancer-specific T cells, I should say, by marshaling what we would consider, you know, an effective T cell repertoire that can then attack cancer. And to remind everyone, when checkpoints show efficacy, it only shows efficacy when the patient has activated T cells already in their body. So our objective is to augment that and to enhance that capability. On the autoimmune side, it's actually the inverse. It's an over-reactive immune system where T cells are self-reactive. They are confused in terms of self versus non-self, and they're attacking the patient's own tissue. So the objective there, we have a couple of approaches, but it's to try to reestablish balance to turn that auto-reactive process off, right?
So, on the oncology side, we have what we call Immuno-STATs. This platform is really based on communicating with T cells the way nature has designed it. That is those purple boxes on the edges, those are co-stimulatory molecules such as IL-2. Well, we all know that IL-2 has had a lot of challenges. Doesn't mean IL-2 is irrelevant. It's actually the molecule that the body uses to stimulate T cells. The question is, how do you stimulate only the T cells that are relevant? That's through that orange, I'm sorry, that yellow circle there in the middle. That is a peptide that binds to the only place where you have specificity on a T cell, and that's the T cell receptor. So that's really the elegance of our platform.
We can dial in specificity, modulate, and alter particular cells that are relevant to the disease state. And this, in the case of cancer, it's tumor-specific T cells. In the case of autoimmunity, it's regulatory T cells, Tregs, and that's our 401 program partner with Ono, or depletion of pathogenic auto-reactive B cells, and that's our 501 molecule. And that's what I'm conveying here. Through this platform, we've basically developed a pipeline of assets. We have a lot more preclinical that I'm not listing here. On the left, we have 101 in the clinic. We've completed phase 1. It's ready for a phase 2 randomized study for HPV-driven cancer. In this case, we focused on head and neck, and we'll go through that in a bit. And 102, what we did is we just swapped out that epitope. It's basically the same drug framework.
And that's for Wilms' tumor 1, which has application to a broad set of solid tumors and hematologic cancers. We're focusing on colorectal, ovarian, pancreatic, and gastric. And then in autoimmunity, we have the 401 program. Again, that's partnered with Ono. We've retained an option for a 50% right in the U.S. market, which actually represents a very large market potential. That drug has potential to be a Humira-like blockbuster in terms of application to a broad spectrum of autoimmune diseases. And then the 500 series, 501, is for targeting auto-reactive B cells. So that's it for the overview, and, you know, we can get into the Q&A.
Terrific. So, you know, first, congratulations because you got several posters or sorry, several presentations for ASCO coming up. One is an oral presentation. And so, you know, I thought investors knew kind of all there is to know about the CUE-101 data. That clearly can't be the case because ASCO wouldn't ask you for an oral presentation, if that was the case. So can you maybe talk to us a little bit about the efficacy and durability data you would like to show, and, and maybe what the key take-home messages are for investors who are going to see this, you know, presentation?
Sure. I'll cover that. The challenge is obviously it's embargoed for ASCO, so I can't go into detail.
Shucks. Yeah.
However, first of all, we're thrilled that it was selected for an oral presentation. I think that underscores the support we have for the impressive data we've generated. It's not any type of real new data that we're going to be presenting, but it's actually just further validating what we've shown. The data strengthens, may even, you know, it's holding and may even strengthen from what has been shown prior. What matters is the overall response rates are holding. Again, if not even, may be improving. What I mean by that is we have patients that have durable, stable disease. You know, that tumor's continuing to shrink, and they look like they may cross that line. We don't know yet.
And so what's important is we've more than doubled the overall response rate of Keytruda alone, which is the standard of care. And it looks like we're moving towards doubling the progression-free survival. Median overall survival is still too early, but the monotherapy data actually bodes very well for the combination where we more than doubled the median overall survival as a monotherapy in second line and beyond. And then the 102 data actually is very similar to 101. We're seeing very similar patterns as monotherapy.
Excellent. You mentioned this in your prepared remarks up to a point. You know, IL-2 has been a little bit of a graveyard. You know, billions of dollars are, you know, have been invested. Investors probably have the scar marks to kind of, you know, show for it. But, you know, I'm kind of curious from those studies as well as your own, what are the learnings that you guys are leveraging, you know, to kind of increase your own probability of success?
Yeah. So, Wren, if you look back when the company was first formed, we were stating from the beginning that our approach was following that's why we call it Cue. It's nature's cues. It's following, you know, the cues that nature's or signals that nature uses. And IL-2 is not meant to be free-floating through the human body. And if it does, it's going to cause a lot of unwanted collateral side effects. And that's one of the real challenges. And yet, despite that general premise, we've had a significant number of companies formed injecting a bolus of IL-2 into a patient, changing some of the isoforms of the molecule. So we have stayed, stayed consistent to what we're doing. And that is we're targeting IL-2 to specific T cell subsets based on the T cell receptor.
And the molecule's been modified so that if it happens to contact an IL-2 receptor without a TCR engagement, it's not going to be there long enough to signal. So we really believe we've created a therapeutic window in a unique way. We can dose the drug multiple doses, very high doses, and where we're not seeing MTDs. We're seeing the desired effect where the specific T cell population we're targeting is amplifying. And we don't have the unwanted side effects. In fact, we've never hit an MTD with this drug. So we're actually really pleased with the data set that we've compiled to date. The frustration is the investment community has seen a lot of high-profile failures and has moved away from, from IL-2. That doesn't negate the importance of IL-2.
IL-2 is what nature uses to stimulate T cells, among other co-stims, but it's a matter of being able to deliver it appropriately. We believe we're achieving that through the design of the molecule by taking advantage of the specificity of the T cell receptor. Anish, do you want to add anything to that?
No, I think it follows on the paradigm of really co-opting the harnessing of the signals between the TCR and the IL-2 that sets it apart. So in a way, you're seeing the cis-targeted IL-2 approach is now coming on where you're trying to be more proximal to T cells. But the immunological constant is that 99.99% of T cells do not have tumor-antigenic specificities. It's a very small fraction of your repertoire. So the issue becomes is how do you guide IL-2 to the right consumer? And if you think about the T cell's identity, the reason you describe a T cell or ascribe it to be tumor-specific is because it has a T cell receptor that's specific for a tumor antigen. So TCR is the entire sort of singular molecule that dictates the T cell's identity.
And so directing it, I think harnessing that specificity allows for the IL-2 to selectively act upon the right T cell that is intended for the reaction. And I think that's what you're seeing playing out with the 101 data and hopefully now with 102 with the early metrics.
Yeah. I think, you know, the other thing is investors can be fickle, and, and things like that. But, but the clinical data continues to improve. There's actually, you know, additional companies that have been formed. Clinicians are very excited to get their hands on, you know, these kinds of molecules for their patients. You've had a, a Type B meeting with the FDA. You, maybe just talk a little bit about that. What was the, the outcome from that? And have there been any sort of additional meetings with the, with the agency since then?
Sure. We haven't had any additional meetings. The Type B meeting, as you conveyed, was very productive. We were impressed by they had a significant team on the call, and it went very well. They gave us good guidance. We are aligned. In essence, they want us to survey two doses. And the reason that's under Project Optimus, which is, you know, particular to immunotherapy where you don't hit MTDs typically. They want to survey at least two doses to see if there's an optimal dose where you're ameliorating possible side effects but also having, you know, the desired effect. We're still confident, with the data sets that we've seen that four mgs per kg is the optimal dose. But we're going to be surveying two doses.
Out of that meeting, we realized a prudent way to address Project Optimus but also generate a body of data early on would be to do a randomized phase 2. 25 patients at one dose of our drug plus Keytruda. 25 patients at the four mg per kg recommended phase 2 dose with Keytruda and then Keytruda alone. This will give us a really solid data set that we're expecting will mirror what we've already seen, to establish a new standard of care. So if we can continue to double the ORR and the PFS and enhance survival, that you know tells you you have a registration path now, with a high, high probability. And that that'll put us in a really good position with both pharma companies and the rest of the platform.
Now, can you remind us what it is you mentioned the doubling of ORR and PFS? What are the numbers, you know, that you would expect from Keytruda, and what are you seeing with your combination?
Historical data with Keytruda, 19% overall response rate in head and neck cancer. Now, that includes both non-HPV and HPV. It's a smaller subset with HPV. You separate those out. It's in the low 20s, like 23%-24%. We're presently with 25 patients at 46%. And that's why I said the data continues to hold, and it may even improve from there. So it looks like we've doubled the overall response rate. What's really relevant there, Wren, is we're seeing equivalent responses in patients with low CPS scores and high CPS scores. And you typically see with Keytruda or other drugs, you typically see, I mean, immunotherapy drugs, better responses in the high CPS because the tumors are already immunologically active. Low CPS, they're not as immunologically active.
We don't see a distinction between them, which tells us we're activating the immune system and we're changing the way the tumor is actually behaving. So that's really encouraging data. The PFS was about 3.4 months for Keytruda. Then what that means is the time, a patient's median times with 50% of patients stay on drug for at least 3.4 months. We look like we're going to be doubling that. The data's still emerging, but it looks very positive to date. Then on the survival, Keytruda's survival data in the historic study was 12.3-12.4 months. Some more recent data as monotherapy has extended that a little bit. We'll keep an eye on that. But based on what we saw as monotherapy, remember second line, Keytruda was 8.4 months. We extended that as a monotherapy to 20.8 months.
So I think it bodes really well in the combination that, you know, we'll see some nice effect there. So we're just very encouraged by these 25 patients. And now we can replicate that in a randomized study. Yeah, that's validating.
So maybe we can talk a little bit about kind of next steps as it pertains to the CUE-101 program. And I guess most importantly, and we've talked about this on, on conference calls, you know, can you provide some context to us regarding, you know, where you are with strategic options that you might want to consider for both the CUE-101 and CUE-102, you know, programs?
Sure. It's a really important question because, you know, we have stayed consistent with our premise and our thesis of the power of what we're, how we're approaching T cell modulation. And that data continues to support. So what we've achieved to date now, we're a small biotech. We're not a large pharma. So what we've achieved to date is we have demonstrated the drug's mechanism. We've demonstrated that it's active. Now, with this phase two, rather than going into a registration path, we just don't have the depth to be able to do a registration path presently. We've designed a phase two that with a defined quantum of capital, a defined quantum of patients, we can basically achieve validation of a new standard of care, very high probability then for success in a registration path. And that validates the whole platform.
So that's why we set it up that way. And then we have 102 behind that, you know, basically emulating what we saw with 101 as a monotherapy. So strategically, we're looking at the whole platform and looking at the various strategic options we have and what's the best use of our internal resources. We could focus on 101. We just don't have the depth to do a 101 phase 2 trial, a 10102 phase 2 trial, and autoimmune. So we're looking at what our options are right now, strategically aligning with third parties with these various asset classes that utilize our skills to their optimum, complementary capabilities from another party, allowing us to still build out the platform. So that's, that's where we are right now. And I've, I've stated it in the past that, you know, we have ongoing dialogue.
Those discussions continue through diligence and, you know, negotiations. So we're confident we'll, in the near term, have some announcements in terms of clarifying what we're doing strategically.
Okay. I've been noticing this with, you know, all of my companies, pretty much all of my companies that I'm talking to, right? I'm the oncology analyst. I'm covering oncology companies, except everybody is, you know, having an autoimmune program in a lot of their pipelines now. And that's great, right? I mean, it's kind of the flip side of the coin, right, when you're dealing with the immune system. And you guys are no exception. You have the CUE-401 study, or asset with Ono. Can you maybe, you know, talk to us, give us a little bit of a status update, of maybe why they partnered it? You know, what did they see?
They appear to be a great partner, but I have no way to kind of gauge it because I don't know where they are, where you are in the development of that drug.
Sure. I'm going to answer it very generically, and I'll have Anish give you the details on the immunology side. I just want to clarify, so we have always had autoimmune. We just never really spoke about it because it was much earlier, and we felt oncology was in the clinic, and that's what was relevant. But it's the flip side of immune modulation. So 401 was a program that, you know, Anish was very much in favor of pushing forward because of its potential. We had a significant number of pharma companies approach us on that program. That's for basically stimulating, inducing Tregs. And we went with Ono because of the structure of the transaction. We have a right to opt in for a 50% collaboration, a 50% ownership in the US, and we will cover 35% of the costs. We also get milestones.
So that's a very attractive program for shareholders. I want to emphasize, it's not a pivot where we're talking about autoimmune right now because the capital markets aren't supporting oncology. We've always had it, which is a good thing. I'll turn it over to Anish just to describe.
Now, this was an asset, Wren, that we created with the intent of generating new populations of regulatory T cells in contrast to other approaches that are focused on preexisting Tregs. Those are the natural IL-2 mutants that are CD25-targeted. So this is a bispecific molecule of an IL-2 and a TGF-beta variant. And the reason for that is those two signals together can convert peripheral CD4 T cells into Tregs. So not only do we act upon existing Tregs, which is what every other IL-2 mutant is trying to do, but we have the potential of generating new populations of Tregs. We've presented some, in the public domain, we've presented early POC data with this in disease models. And with Ono, that has continued to mature and now showing activity across several different disease models.
So it's really a very exciting time for that program, but also very differentiated from the way others have sort of approached the domain. It actually gives you an opportunity to immune reset if you could convert your pathogenic T cell repertoire into a regulatory phenotype. So it's a fundamentally very different way of looking at disease, in that sense. And then besides that, we've got, we just disclosed in our last call, and this is a program we've been working on for about over a year, the CUE-500 series, where you can achieve deep depletion of B cells, that's T cell mediated, but avoid the CAR-T route and do it with a biologic. So this is an Immuno-STAT that can redirect your protective antiviral T cells, which are nature's memory killer T cells that all of us have harbored for decades.
These are T cells specific for SARS-CoV-2, for CMV, for flu. We can redirect them to recognize B cells and kill them. So that's a very tailored way of harnessing a small population of T cells to do the job as opposed to pan-T cell engagers that are anti-CD3-based that activate every T cell. And then you have the sort of tricky outcome of tolerability and toxicities and safety concerns. So CUE-500 essentially is a pipeline and a product for B cell depletion across every single disease that people are focused on, B cells, all the way from urology, dermatology, rheumatology, endocrine autoimmunity, all the way through transplantation, even allergies and such. So those are the two major focuses of the autoimmune programs. CUE-401 is further advanced with the Ono collaboration.
501, we've just released early data, and we'll be talking more about that as this year goes by.
So just to go back, and I appreciate the correction, you know, regarding the fact that you guys had this autoimmune program, you know, the entire time, which also, you know, kind of highlights, I think that it's more of a, you know, a company focused on immunology, right, as a broad strokes, more than just focused on, let's say, cancer. Just going back to Ono real quick, can you give us a sense as to, you know, is this one of those collaborations where you're pretty actively involved, or is this something where they're really driving the ship and you kind of just get an update?
Now, this has been a wonderful collaboration. All the research is essentially driven by us. Ono has supported all of the research costs, FTE costs, pass-through costs. Essentially, it's a fully funded program till we get into the opt-in decision, which we anticipate in the second half of this year. And then you start the IND enabling activities where obviously collectively with them we'll be mapping out. And some of those discussions have already started. But so far, the research driving, again, the molecular bases and all the fundamental data is all driven by Cue.
Okay.
On this end. They've been great colleagues with us, just regular meetings back and forth through the science review teams and JSC mechanisms.
Got it. So the 500 series, you know, you mentioned it first kind of came out, I think it was in the last conference call, if I'm remembering correctly, you know, targeting B cell, you know, malignancies. I didn't understand entirely how exactly you're converting these, you know, already nascent memory T cells.
Yeah.
To then go after CD19. So maybe in layman's terms.
Yeah. So in layman's terms, it's an Immuno-STAT that has a virus peptide to a T cell epitope.
Okay. So a viral T cell epitope, a flu epitope, a SARS-CoV-2. And it's instead of having the IL-2, where the Immuno-STAT didn't in the structure that Dan showed you, you have an scFv to a B cell antigen like CD19. So you essentially end up painting the B cell with viral pHLA complexes. So you make the B cell appear, and you trick the immune system into believing that the B cell appears like a virally infected cell, hence is selectively attacked by these virus-specific memory cells that are all over our body in tissue and lymphoid organs. So that's a very sort of very simple way of explaining the concepts in Immuno-STAT with a virus pHLA that sticks to the B cell via CD19 mechanism.
As you think about moving this program forward, is it, you know, because of the opportunity, and it's still early on, it's something that you really want to move forward on your own, or are you already, you know, evaluating strategic options?
We've had a fair bit of inbound interest when we first started talking about this program, and we remain engaged in those discussions. These are mostly large pharma partners. I think a large reason for that is, in many ways, the Immuno-STAT concept is validated from the oncology data set where we've dosed over 120 patients. So this is a different Immuno-STAT. The second, and perhaps the more important reason is the 500 series is significantly differentiated from other mechanisms of B-cell depletion, ADCC mechanisms, CAR-T mechanisms, and the pan-T-cell engager mechanisms, both on the safety and tolerability, but also sensitivity. So that's been a big driver of the conversations we are engaged in.
I think, you know, when you look at B cells as a target, it creates an extraordinary opportunity in autoimmune diseases as it's becoming apparent now with some of the data that's emerging from the more recent approaches.
Got it. So on the last, call it 1 minute, kind of, you know, can you remind us what's the cash position? And then probably even more importantly to us, what's the data? We know the ASCO data, obviously. We talked about that. But even from the 401 and 500 series, you know, group of assets, what might be the data or cadence of data we might see over the next 6-12 months?
Sure. I'll touch the cash position runway, some of the strategic milestones, and I'll have Anish talk about the data that'll be coming out. So, on a cash position, we entered the quarter with about $40 million. That'll take us, you know, into Q1 2025. So clearly, you know, we're going to have to capitalize. We're in deep discussions strategically. So we're looking at consummating, you know, one or several strategic alignments that will enhance our capability and extend the runway. The 101 data, obviously, we have ASCO coming up with, with 102. 401, I think the real important metric there is Ono selection and our opt-in on the co-development option, whether we do that or not. And the milestone levels we get are going to be based on whether we opt in. And 501, it's, you know, based on the data we have.
We have ongoing dialogue with several pharma companies. What we end up doing strategically is based on what we feel we're best suited to further exploit and create as much value by holding onto assets, take them along, you know, further along. All it's going to be based on is cost of capital and, you know, capital access.
Anish, maybe in 30 seconds, do we have any scientific presentations that are coming up in the next?
We have two this week at PEGS, and we will be looking at meetings in the second half of the year to present both the autoimmune B cell side of things as well as trying to get some of the more recent 401 animal disease model data out there.
Excellent. Well, thank you guys very much for the time.
Thank you, Wren.
I really appreciate it.
Thanks, Wren.